What are the malignant causes of lymphadenopathy and pleural effusion?

Malignant Causes of Lymphadenopathy and Pleural Effusion

The most common malignant causes of concurrent lymphadenopathy and pleural effusion are lung cancer, breast cancer, and lymphoma, with lung cancer accounting for approximately one-third of all malignant pleural effusions. 1

Primary Malignant Etiologies

Lung Cancer

• Most common cause of malignant pleural effusions (25-52% of all cases)
• Typically presents with moderate to large unilateral effusions (500-2,000 ml)
• Often associated with mediastinal lymphadenopathy
• Mechanism: direct pleural invasion, lymphatic obstruction, or tumor emboli to visceral pleura 1
• Hemoptysis with pleural effusion is highly suggestive of bronchogenic carcinoma 1

Breast Cancer

• Second most common cause (3-27% of malignant pleural effusions)
• Higher prevalence in patients with disseminated disease (36-65%)
• Often presents with ipsilateral pleural effusion and axillary lymphadenopathy
• Mechanism: direct extension, lymphatic spread, or hematogenous metastasis 1

Lymphoma

• Both Hodgkin's and non-Hodgkin's lymphoma are significant causes (12-22% of cases)
• 30% of patients with lymphoma and pleural effusions have CT evidence of pleural involvement 2
• 70% of lymphoma patients with pleural effusions have mediastinal lymphadenopathy 2
• Extrapleural disease is common (found in 30% of lymphoma patients with effusions) 2
• Posterior mediastinal disease frequently associated with extrapleural involvement 2

Other Malignancies

• Ovarian cancer
• Gastrointestinal carcinomas
• Mesothelioma (incidence varies geographically)
• Unknown primary (5-10% of malignant effusions) 1

Radiographic Findings

Pleural Effusion Characteristics

• Malignant effusions typically present as exudates (rarely transudates) 1
• Massive effusions (occupying entire hemithorax) are most commonly due to malignancy 3
• Radiographic signs include:
  • Homogeneous opacity over affected hemithorax
  • Mediastinal shift away from affected side (absence suggests fixed mediastinum or endobronchial obstruction)
  • Blunting of costophrenic angles
  • Obscured hemidiaphragm silhouette 3

Lymphadenopathy Patterns

• Mediastinal lymphadenopathy is common in malignant pleural effusions
• In lymphoma, parietal pleural disease (thickening or nodules) is seen in 23% of cases with effusions 2
• Right paratracheal and subcarinal areas are commonly involved in lymphadenopathy 4
• Malignant lymphadenopathy often involves multiple sites and can exceed 2cm in size 4

Pathophysiologic Mechanisms

1. Direct tumor involvement of pleura (common in lung cancer, mesothelioma, breast cancer)
2. Lymphatic obstruction between parietal pleura and mediastinal lymph nodes
3. Hematogenous spread to parietal pleura
4. Tumor emboli to visceral pleural surface with secondary seeding to parietal pleura
5. Local inflammatory changes causing increased capillary permeability 1

Paramalignant Effusions

These are effusions related to malignancy but not from direct pleural involvement:

• Postobstructive pneumonia with parapneumonic effusion
• Thoracic duct obstruction causing chylothorax
• Pulmonary embolism
• Transudative effusions from atelectasis or hypoproteinemia
• Treatment-related (radiation therapy, chemotherapeutic agents like methotrexate, procarbazine, cyclophosphamide, bleomycin) 1

Diagnostic Approach

• Thoracic CT and ultrasound are essential for distinguishing malignant from benign effusions 5
• Ultrasound is superior for assessing internal characteristics and identifying septations 3
• Diagnostic thoracentesis should be performed in any patient with unilateral effusion or bilateral effusion with normal heart size 1
• Pleural fluid analysis should include:
  • Cytology (diagnostic in about 60% of cases)
  • Cell count and differential (lymphocyte or mononuclear cell predominance is typical)
  • Chemistry (protein, LDH, glucose, pH, amylase)
• Pleural biopsy may be necessary in cytology-negative cases 6
• Low pleural fluid pH (<7.30) and glucose (<60 mg/dl) may indicate higher tumor burden 1

Clinical Presentation

• Dyspnea is the most common symptom (>50% of cases)
• Constitutional symptoms: weight loss, anorexia, malaise
• Chest pain (particularly in mesothelioma) - typically dull and aching rather than pleuritic
• Presence of malignant effusion indicates advanced disease and poor survival 5
• In lung cancer, malignant pleural effusion upstages the disease to stage 4 5

The presence of both lymphadenopathy and pleural effusion should raise high suspicion for malignancy, particularly lung cancer, breast cancer, or lymphoma, and warrants thorough diagnostic evaluation.